e Staphylococcus aureus is a major cause of food poisoning outbreaks associated with dairy products, because of the ingestion of preformed enterotoxins. The biocontrol of S. aureus using lactic acid bacteria (LAB) offers a promising opportunity to fight this pathogen while respecting the product ecosystem. We had previously established the ability of Lactococcus lactis, a lactic acid bacterium widely used in the dairy industry, to downregulate a major staphylococcal virulence regulator, the accessory gene regulator (agr) system, and, as a consequence, agr-controlled enterotoxins. In the present paper, we have shown that the oxygenindependent reducing properties of L. lactis contribute to agr downregulation. Neutralizing lactococcal reduction by adding potassium ferricyanide or maintaining the oxygen pressure constant at 50% released agr downregulation in the presence of L. lactis. This downregulation still occurred in an S. aureus srrA mutant, indicating that the staphylococcal respiratory response regulator SrrAB was not the only component in the signaling pathway. Therefore, this study clearly demonstrates the ability of L. lactis reducing properties to interfere with the expression of S. aureus virulence, thus highlighting this general property of LAB as a lever to control the virulence expression of this major pathogen in a food context and beyond.S taphylococcus aureus is a major cause of food poisoning outbreaks associated with dairy products, because of the ingestion of staphylococcal enterotoxins preformed in foodstuff (1). In fermented milk products, a strategy to combat S. aureus or any other pathogen must respect the product ecosystem, which is crucial to the manufacturing process and the development of the organoleptic properties of the final product. Biocontrol based on the use of nonpathogenic lactic acid bacteria (LAB) appears to be an attractive and sustainable strategy to combat bacterial pathogens. The ability of LAB to inhibit S. aureus growth has been reported in several contexts (2-6) and relies on properties such as acidification, the production of bacteriocins and hydrogen peroxide, or competition for nutrients (3, 6-10). LAB are also reportedly able to interfere with the expression of S. aureus virulence, which includes staphylococcal enterotoxin production (9,11,12). However, with just a few exceptions (12), the inhibitory mechanisms underlying this inhibition of virulence are still poorly understood.We previously investigated the interaction between Lactococcus lactis LD61 and S. aureus MW2 and established that L. lactis downregulated the expression of the accessory gene regulator (agr) system of S. aureus in mixed cultures as well as agr-controlled enterotoxins such as enterotoxin C (13,14). This agr downregulation by L. lactis was observed under planktonic conditions, in chemically defined medium (CDM) at a constant of pH 6.6 and under microaerobic conditions, and was further validated under sessile growth conditions in a model cheese (15). The agr system is a key virulence regulator ...